What is the best treatment approach for a patient diagnosed with Graves' disease, considering factors such as age, sex, and medical history?

Treatment of Graves' Disease

Methimazole is the preferred first-line treatment for most patients with Graves' disease, administered for 12-18 months with dose titration based on thyroid function tests. 1, 2, 3

Initial Treatment Strategy

Start with methimazole as the primary antithyroid medication for newly diagnosed Graves' disease, as it is FDA-approved for this indication and recommended by multiple guideline bodies. 1, 2 The standard treatment protocol involves:

• 12-18 month course of methimazole therapy with monitoring every 4-6 weeks initially, then every 2-3 months once stable 1, 3
• Titrate dose to maintain FT4 in the high-normal range using the lowest effective dose 1
• Monitor for adverse reactions within the first 90 days, when agranulocytosis and hepatotoxicity are most likely to occur 4

Methimazole is preferred over propylthiouracil (PTU) because of its longer half-life allowing once-daily dosing, which improves adherence. 5 Approximately 50% of patients achieve remission after completing this course. 4

Symptomatic Management

Add beta-blockers for immediate symptomatic relief of tachycardia, tremor, and anxiety while awaiting antithyroid drug effect. 1 This adjunctive therapy addresses the adrenergic symptoms without treating the underlying hyperthyroidism. 5

Monitoring Protocol

Check thyroid function every 2-3 weeks initially after diagnosis, then extend to every 4-6 weeks once stable. 1 This frequent monitoring is critical to:

• Catch the transition from hyperthyroidism to hypothyroidism, which commonly occurs and is a frequently missed pitfall 1
• Adjust medication dosing appropriately 1
• Detect treatment failure early 3

Decision Point at 12-18 Months

Measure TSH receptor antibodies (TSH-R-Ab) at 12-18 months to guide next steps. 3 The decision algorithm is:

• If TSH-R-Ab persistently elevated: Either continue methimazole for another 12 months with repeat antibody measurement, or proceed to definitive therapy (radioactive iodine or thyroidectomy) 1, 3
• If TSH-R-Ab normalized: Consider discontinuing methimazole and monitoring for relapse 3

For patients over 35 years old, long-term low-dose methimazole (2.5-5 mg daily) reduces relapse risk compared to drug discontinuation. 6 This is particularly relevant for older patients who may not tolerate relapse well.

Definitive Treatment Options

Radioactive iodine (RAI) or thyroidectomy should be offered when:

• Patient relapses after completing antithyroid drug course 1
• Patient does not respond to antithyroid medications 1
• Very large goiters are present 1
• Concomitant suspicious or malignant thyroid nodules exist 4
• Coexisting hyperparathyroidism requires surgical correction 4
• Moderate to severe thyroid eye disease is present (thyroidectomy preferred over RAI) 4

Radioactive Iodine Considerations

RAI is contraindicated in pregnancy and breastfeeding, and patients must not breastfeed for four months after RAI treatment. 1 Additionally:

• RAI is contraindicated in active/severe orbitopathy 3
• Steroid prophylaxis is warranted for patients with mild/active orbitopathy receiving RAI to prevent worsening of eye disease 3
• RAI causes development or worsening of thyroid eye disease in 15-20% of patients 4
• Hypothyroidism is an inevitable consequence requiring lifelong levothyroxine replacement 5

Thyroidectomy Considerations

Thyroidectomy should be performed by an experienced high-volume thyroid surgeon to minimize complications. 3 Potential complications include:

• Hypoparathyroidism 4
• Vocal cord paralysis from laryngeal nerve damage 4, 5
• Lifelong hypothyroidism requiring levothyroxine replacement 5

Special Population: Pregnancy

Women planning pregnancy or in first trimester must switch from methimazole to propylthiouracil due to teratogenic risk of methimazole. 1 After the first trimester, consider switching back to methimazole. 1 The goal is to maintain maternal FT4 in the high-normal range using the lowest possible dose. 1

Some women opt for definitive therapy with RAI or surgery prior to pregnancy to avoid antithyroid drug exposure during gestation. 4

Thyroid Storm Management

Hospitalize immediately for intensive management if thyroid storm is suspected. 1 Treatment includes:

• High-dose antithyroid drugs 1
• Beta-blockers for symptomatic control 1
• Corticosteroids 1
• Saturated solution of potassium iodide (SSKI) 1

Critical Pitfalls to Avoid

Do not fail to recognize the transition from hyperthyroidism to hypothyroidism, which is common especially with thyroiditis. 1 This requires the frequent monitoring schedule outlined above.

Do not overlook ophthalmopathy or thyroid bruit on physical examination, as these findings are diagnostic of Graves' disease and influence treatment decisions. 1

Do not use radioactive iodine in pregnant or breastfeeding women under any circumstances. 1

Do not assume all patients under 35 years will achieve durable remission—younger patients have higher relapse rates and may benefit from earlier consideration of definitive therapy. 6